8G2N

Crystal structure of Tetrahymena thermophila G-rich DNA with novel ligand PyDH2

8G2N の概要

• エントリーDOI: 10.2210/pdb8g2n/pdb
• 分子名称: G-rich DNA, 4,4'-{pyridine-2,6-diylbis[carbonyl-(1E)-hydrazin-2-yl-1-ylidene-(E)-methanylylidene]}bis(1-methylquinolin-1-ium), MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: g-quadruplex dna, ligand intercalation, four tetrads, dna
• 由来する生物種: Tetrahymena thermophila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8832.58

構造登録者

Martin, K.N.,Yatsunyk, L.A. (登録日: 2023-02-06, 公開日: 2024-02-14, 最終更新日: 2025-09-17)

主引用文献

Martin, K.N.,Lam, G.,Reznichenko, O.,Brunner, K.E.,Zdilla, M.J.,McCarthy, S.E.,Granzhan, A.,Yatsunyk, L.A.
Conformational Change in a Four-Tetrad DNA G-Quadruplex upon Intercalation of a Small-Molecule Ligand PyDH2.
Angew.Chem.Int.Ed.Engl., 64:e202501443-e202501443, 2025

PubMed Abstract: G-quadruplexes (G4s) are non-canonical DNA structures implicated in a number of biological processes. Small-molecule ligands can alter stability and folding of G4s, which can potentially be exploited for therapeutic purposes. In this work, we investigate the interaction of telomeric DNA fragment from Tetrahymena thermophila (TET25, 5'-G(TTGGGG)3') with a G4 ligand PyDH2 belonging to the bisquinolinium family. When alone, TET25 adopts a mixture of three conformations, with the most abundant being a four-tetrad hybrid G4. In the presence of PyDH2, surprisingly, TET25 folds into an antiparallel chair G4, with PyDH2 intercalated between G-tetrads 2 and 3, according to our crystal structure. The structure represents the second example, and the first crystallographic evidence, of ligand intercalation into a G4. In solution, the interaction of PyDH2 and TET25 leads to a number of complexes differing by G4 topology and binding stoichiometry, strong stabilization of G4 (∆T = 12.4 °C in the presence of one equiv. of PyDH2) and large hysteresis of ∼10 °C, suggesting that ligand binding and G4 folding processes are complex.

PubMed: 40403170
DOI: 10.1002/anie.202501443

実験手法

X-RAY DIFFRACTION (1.33 Å)